Objective To evaluate the lethal effect of adenovirus-mediated Ad-hTERTp-HSV-TK/GCV suicide gene system in combination with oxaliplatin (L-OHP) on human hepato carcinoma cell line HepG2 in vitro.Methods It was used that the replication-defective adenovirus carring the HSV-TK gene under control of the hTERT promoter to transfer the HepG2 cells in vitro. Human hepato carcinoma cell line HepG2 was transfected with MOI=100. It was studied that the grow inhibitory effct with Ad-hTERTp-HSV-TK/GCV therapy, oxaliplatin, Ad-hTERTp-HSV-TK/GCV therapy in combination with oxaliplatin through different drug concentration on human hepato carcinoma cell line HepG2. The growth inhibition rate of HepG2 cells was determined by trypan blue exclusion assay and MTT.Results The growth of HepG2 cells Ad-hTERTp-HSV-TK/GCV, oxaliplatin, and combination of Ad-hTERTp-HSV-TK/GCV and oxaliplatin was significantly slower.The more concentration the greater inhibition of cell growth. The growth inhibition rate of combined Ad-hTERTp-HSV-TK/GCV with oxaliplatin was 86.63 %.The growth inhibition rate of Ad-hTERTp-HSV-TK/GCV was 72.12 % compared to the combined therapy (P =0.023). The growth inhibition rate of oxaliplatin was 59.41% compared to the combined therapy (P =0.019). Combination of Ad-hTERTp-HSV-TK/GCV and oxaliplatin resulted in greater inhibition of cell growth compared with TK gene and L-OHP (P ＜0.05).Conclusion HSV-TK/GCV in combination with L-OHP can enhance thelethal effect of suicide gene therapy against HepG2 cells.It is more targetable than the function of single drug therapy.Also, it could reduce drug level and plays an important role on the future's clinical medication.

Objective To observe the effect of Ad-bTERTp-HSV-TK/GCV system on malignant ascites of mice and probe into its mechanism of action.Methods The SX1 inbred strain mice were injected with H22 cell line of liver cancer and were divided into 4 groups at random.The mice in each group were given corresponding treatment after 48 hours.The production of ascites and survival period were evaluated. The apoptosis rates of tumor cells were detected by FCM.Morphological changes of tumor cells were studied by electromicroscope.Results Compared with other groups.Ad-hTERTp-HSV-TK/GCV Can obviously inhibit the production of ascites(P<0.01),prolong the survival period (P<0.01),and apoptosis rate in this group (27.12±2.12)% was significantly higher than that in other groups.No obvious side effect Was found during the treatment.Conclusion Ad-hTERTp-HSV-TK/GCV system Can inhibit production of ascites and prolong the survical period of mice by inducing apoptosis of hepatoma cells,which is a safe and feasible treatment for hepatoma therapy.

Objective To investigate the effect of 5-Aza-CdR on Notch1 pathway and neural regeneration and to explore the effects of 5-Aza-CdR on learning memory ability in mice by exploring active avoidance behavior.Methods Sixty 6～8-week-old SPF-grade ICR male mice were divided into two groups.5-Aza-CdR was administered to one group of mice via lateral ventricular injection,while the control group was injected with bovine serum albumin.Notch1 and HES1 mRNA and protein expression levels were detected by Real-time PCR and Western blot 24 hours after injection;5-bromo-2'-deoxyuridine-positive cells were observed by laser confocal microscopy,and Notch1 expression in hippocampal dentate gyrus was viewed with laser confocal microscopy.Notch1 methylation changes were detected by ethylation-specific PCR,and learning and memory behaviors of mice were assessed by passive avoidance tests and shuttle avoidance assays.Results Injection of 5-Aza-CdR increased hippocampal Notch1 pathway activity,promoted neuronal regeneration in the DG region,decreased methylation levels in the Notch1 promoter region,and enhanced the ability of mice to perform active avoidance behavior.Conclusions The effect of 5-Aza-CdR on active avoidance behavior may be related to the influence of hippocampal neural regeneration through the Notch 1 pathway.